The persistent high incidence of limb loss resulting from advanced forefoot tissue loss and infection in diabetic patients prompted an evaluation of transmetatarsal (TMA) and transtarsal/midfoot amputations in achieving foot salvage at our tertiary vascular practice. Over the last 8 years, 74 diabetic patients required 77 TMAs for tissue loss and/or infection. Twelve (16%) of the patients had a contralateral below-knee amputation (BKA) and 26% (n = 20) had dialysis-dependent renal failure. Thirty-five (45%) limbs had concomitant revascularization (bypass grafting or percutaneous transluminal angioplasty), 32 (42%) had arterial occlusive disease by noninvasive testing and/or arteriography but were not or could not be revascularized, and seven (13%) had normal hemodynamics. Patient factors, arterial testing, operative complications, operative mortality (<60 days), wound healing (at 90 days), limb salvage, functional status, and survival were evaluated during a mean follow-up of 20 months (range 3-48). Operative mortality was 5% (n = 4) after TMA and/or midfoot amputation. Although 32 TMAs initially healed (44%), six BKAs were required 5-38 months later. Of the 41 nonhealing TMAs (56%), progressive infection/tissue loss necessitated major amputation of nine limbs. Chopart (n = 22) or Lisfranc (n = 10) midfoot amputations were done in the remaining 32 nonhealing TMAs. Despite additional wound revisions in 14 patients (44%), major amputation was needed in six limbs. However, functional ambulation was achieved in 23 of 25 (92%) limbs with healed midfoot amputations, and foot salvage was possible in 61% (25/41) of nonhealing TMAs. Overall limb salvage for TMA/midfoot procedures was estimated from Kaplain-Meier life tables to be 73%, 68%, and 62% at 1, 3, and 5 years, respectively, with only 50% of dialysis patients avoiding major amputation. Ankle pressure >100 mm Hg and a biphasic pedal waveform had a positive predictive value (PPV) of 79%, and toe pressure >50 mm Hg had a PPV of 91% for determining healing of TMA/midfoot amputations. One- and 3-year survival rates were only 72% and 69% for the entire cohort from life table estimates. Aggressive attempts at foot salvage are justified in diabetic patients with advanced forefoot tissue loss/infection after assuring adequate arterial perfusion. Transtarsal amputations salvaged over half of nonhealing TMAs with excellent functional results.